Peripheral mediators involved in gastric hyperemia to vagal activation by central TRH analog in rats.
Mechanisms mediating the increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a gastric acid secretory dose (30 ng) were investigated using hydrogen gas clearance in urethan-anesthetized rats. The histamine H1 receptor antagonist pyrilamine (intravenously), capsaicin (subcutaneously, 10 days), and NG-nitro-L-arginine methyl ester (L-NAME, intracisternally) failed to impair the 150% rise in GMBF induced by intracisternal injection of RX-77368. By contrast, atropine (subcutaneously) and NG-monomethyl-L-arginine (intravenously) completely inhibited the increase in GMBF evoked by intracisternal RX-77368. L-NAME (intravenously) blocked the intracisternal RX-77368-induced increase in GMBF in capsaicin-pretreated rats, and the L-NAME effect was reversed by intravenous L- but not D-arginine. These findings indicate that vagal efferent activation induced by TRH analog injected intracisternally at a gastric acid secretory dose increases GMBF through atropine-sensitive mechanisms stimulating L-arginine-nitric oxide pathways, whereas H1 receptors and capsaicin-sensitive afferent fibers do not play a role.
Király
A
A
Center for Ulcer Research and Education, West Los Angeles Veterans Affairs Medical Center, California, USA.
Sütö
G
G
Guth
P H
PH
Taché
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002946:Cisterna Magna / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation; D006940:Hyperemia; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013238:Stereotaxic Techniques; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001285:Atropine; D001120:Arginine; D002211:Capsaicin; D011761:Pyrrolidonecarboxylic Acid; D019331:NG-Nitroarginine Methyl Ester